Improvement of Symptoms After Removal of the Essure® Contraceptive Implant
- Conditions
- Implant ComplicationContraceptive Device; Complications
- Interventions
- Device: Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examinationBiological: blood sampleBiological: urine collectionBiological: Collection of a lock of hairOther: questionnaire
- Registration Number
- NCT06355713
- Lead Sponsor
- Hospices Civils de Lyon
- Brief Summary
ESSURE® is an implantable medical device for definitive and irreversible sterilization indicated for adult women of childbearing age. These implants are inserted into the fallopian tubes by hysteroscopy. Marketed in 2002, ESSURE® contraceptive implants were withdrawn from the French market in 2017 (and worldwide in 2017 and 2018) following the observation in certain patients of polymorphic and non-specific gynecological and extra-gynecological symptoms. Studies with small numbers and short-term follow-up have shown a significant improvement in these symptoms after implant explantation. This constitutes a real public health problem since according to the report of the EPI-PHARE Scientific Interest Group, 198,000 French women have these implants and only 30,000 of them, or 15%, have been explanted, knowing that explantation of ESSURE® implants is recommended only in symptomatic patients. A large number of these patients, presenting symptoms, have not yet been treated for an explant.
The physiopathological mechanism(s) is (are) not yet determined but several arguments are in favor of a dissemination of metallic elements contained in these implants whose accumulation could lead to inflammatory and/or allergic and/or autoimmune phenomena.
Carrying out a prospective study with long-term longitudinal follow-up appears essential to precisely assess the degree of improvement in the symptoms and quality of life of these patients, determine the most appropriate surgical techniques, and understand the pathophysiological mechanisms that may result in the implementation of specific treatments and relevant markers. From a surgical point of view, there is a real risk of fracture of implants whatever the type of intervention performed: study the biomechanical properties of implants with a view to characterizing their behavior to mechanical rupture but also their thermal resistance in an objective manner seems essential to limit the risk of fracture and help to inform the patient about the surgical technique proposed for explantation. From a biological point of view, the dosage of the metallic elements constituting ESSURE® implants and potentially toxic ones could make it possible to objectify the release of these metallic elements in the body. Analysis of pro-inflammatory cytokines, micro-RNAs (miRNA), quantitative analysis of inflammatory pathway messenger ribonucleic acid (mRNAs) (NanoString technology) and analysis of neuroinflammation by functional imaging should make it possible to explore potential pathophysiological mechanisms. This study responds to a significant request from patient associations.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 444
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Group Collection of a lock of hair Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication Control Group blood sample Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication Control Group urine collection Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication Essure Group urine collection Patients requiring removal of the Essure® contraceptive implant Essure Group Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination Patients requiring removal of the Essure® contraceptive implant Essure Group questionnaire Patients requiring removal of the Essure® contraceptive implant Control Group Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication Essure Group blood sample Patients requiring removal of the Essure® contraceptive implant Essure Group Collection of a lock of hair Patients requiring removal of the Essure® contraceptive implant Control Group questionnaire Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication
- Primary Outcome Measures
Name Time Method Percentage of patients with improvement in symptoms Percentage of patients with improvement in symptoms At 2 months after surgical intervention (removal of the Essure® contraceptive implant) Percentage of patients with a score of 1, 2 or 3 (corresponding to improvement in symptoms) on the Patient Global Impression of Improvement (PGI-I) scale.
The PGI-I is a transition scale that is a single question asking the patient to rate their symptoms now, as compared with how it was prior to before beginning treatment on a scale from 1 = Very much better to 7 = Very much worse.
- Secondary Outcome Measures
Name Time Method Fibromyalgia Impact Questionnaire (FIQ) score up 5 years quality of life of women with fibromyalgia symptoms (from 0 : no symptoms to 100 : important symptoms)
Multidimensional Fatigue Inventory (MFI)-20 score up 5 years Fatigue assessment according to 5 dimensions (General Fatigue, Physical and Mental Fatigue, Reduction in Motivation and Activities) (score from 20 : no fatigue to 100 : important fatigue)
Visual analog scale (VAS) score up 5 years pain assessment (from 0 : no pain to 100 : unbearable pain)
visual analog scale (VAS) score During surgical intervention Assessment by the surgeon of the difficulty of performing the ablation on a visual analog scale : from 0 (very easy) to 100 mm (very difficult)
Questionnaire Douleur St-Antoine (QDSA) score up 5 years Assessment of sensory impact of pain (from 0: no pain to 36: important impact) and emotional impact of pain (from 0: no pain to 28 : important impact). The global score ranges from 0 to 64.
Female Sexual Function Index (FSFI) score up 5 years quality of sexual life (from 2 to 36). A low score indicates poorer sexual function.
characterization of the mechanical behavior of the implant During surgical intervention characterization of the mechanical behavior of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)
determination of the associated mechanical stress levels determination of the associated mechanical stress levels During surgical intervention determination of the associated mechanical stress levels of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)
Percentage of patients with improvement in symptoms up 5 years Percentage of patients with a score of 1, 2 or 3 (corresponding to improvement in symptoms) on the PGI-I scale.
The PGI-I is a transition scale that is a single question asking the patient to rate their symptoms now, as compared with how it was prior to before beginning treatment on a scale from 1 = Very much better to 7 = Very much worse.Short Form 12 (SF-12) score up 5 years quality of life with assessment of the physical dimension (from 9.94738 to 70.02246) and the mental dimension (from 5.89058 to 71.96825). For each, the average in the general population is 50.
Hospital Anxiety and Depression scale (HADS) score up 5 years anxiety dimension and depressive dimension (for each dimension, from 0 : no symptom to 21 : certain symptomatology)
Higham questionnaires up 5 years The Higham score is used to quantify blood loss during menstruation. A score ≥ 100 indicates a loss of 80 ml or more, which defines menorrhagia. A score ≥ 150 may indicate an indication for surgery for menometrorrhagia.
Duration of the procedure During surgical intervention Duration of the procedure (calculated between incision and closure) in number of minutes
Complications Up to 2 months after the operation Number and types of per- and post-operative complications
quantification of the factors influencing these levels of mechanical stress During surgical intervention quantification of the factors influencing these levels of mechanical stress of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)
Concentrations of titanium constituting the Essure® implant up 12 months after surgical intervention Concentrations of titanium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Concentrations of nickel constituting the Essure® implant up 12 months after surgical intervention Concentrations of nickel constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Concentrations of chromium constituting the Essure® implant up 12 months after surgical intervention Concentrations of chromium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Concentrations of tin constituting the Essure® implant up 12 months after surgical intervention Concentrations of tin constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
thermal resistance During surgical intervention The thermal resistance of the Essure® device implant during coagulations/electrical sections will be assessed.
risk of degradation During surgical intervention The risk of degradation depending on the temperature f the Essure® device implant used during coagulations/electrical sections will be assessed.
Concentrations of molybdenum constituting the Essure® implant up 12 months after surgical intervention Concentrations of molybdenum constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Concentrations of manganese constituting the Essure® implant up 12 months after surgical intervention Concentrations of manganese constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
concentration of pro-inflammatory cytokines Up 2 months after surgical intervention concentration of pro-inflammatory cytokines in the blood will be assessed
analysis of inflammatory pathway mRNAs Up 2 months after surgical intervention analysis of inflammatory pathway mRNAs (nanostring® technology) in a pathology sample from the surgical specimen will be assessed.
Concentrations of platinum constituting the Essure® implant up 12 months after surgical intervention Concentrations of platinum constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Concentrations of iridium constituting the Essure® implant up 12 months after surgical intervention Concentrations of iridium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Concentrations of silver constituting the Essure® implant up 12 months after surgical intervention Concentrations of silver constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Concentrations of iron constituting the Essure® implant up 12 months after surgical intervention Concentrations of iron constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
Functional brain functions up 6 months after Surgical intervention MRI-PET (Magnetic resonance imaging- Positron Emission Tomography) examination :
* Mapping of brain inflammation: binding potential mapping of \[11C\]PK11195 characteristic of activated microglia
* Brain anatomical imaging: clinical type anatomical MRI examination to assess the presence of cerebral anatomical abnormality
* Brain mapping of functional connectivity at rest using Functional magnetic resonance imaging (fMRI)
* Brain mapping of structural connectivity by diffusion MRI
* Perfusion imaging : perfusion MRI examination without contrast product to assess the presence of cerebral perfusion abnormality
* Magnetic susceptibility imaging: to detect possible hemorrhagesConcentrations of tungsten constituting the Essure® implant up 12 months after surgical intervention Concentrations of tungsten constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).
expression profile of miRNAs Up 2 months after surgical intervention Expression profile of miRNAs in the peritoneal fluid will be assessed.
activated T lymphocyte profile Up 2 months after surgical intervention activated T lymphocyte profile in blood will be assessed.
Percentage of detection of Human Leukocyte Antigen Up 2 months after surgical intervention Percentage of detection of Human Leukocyte Antigen (HLA)-DR53 (DRB4∗01) associated with nickel allergies in blood will be assessed.
Trial Locations
- Locations (10)
CHU de Rouen
🇫🇷Rouen, France
CHU de Angers
🇫🇷Angers, France
Hôpital Femme Mère Enfant (Hospices Civils de Lyon)
🇫🇷Bron, France
Hôpital Bicêtre
🇫🇷Le Kremlin-Bicêtre, France
Hôpital Jeanne de Flandres
🇫🇷Lille, France
Hôpital de La Conception
🇫🇷Marseille, France
Institut Mère Enfant Alix de Champagne, CHU Reims
🇫🇷Reims, France
Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France
Hôpital Paule de Viguier, CHU de Toulouse
🇫🇷Toulouse, France
Hôpital André Mignot, Centre Hospitalier de Versailles
🇫🇷Versailles, France